This project is designed to investigate the feasibility of transplanting pancreatic islet tissue to diabetic recipients in an attempt to ameliorate diabetes. Diabetic recipients are selected from a population of patients that have previously undergone kidney transplantation for treatment of end stage renal failure and who are already receiving immunosuppressive therapy. Pancreatic islet tissue is prepared by collagenase digestion of the donor pancreas. Purified islet tissue was used in an initial series. Ten transplants were performed in 7 patients. None were completely ameliorated of diabetes. In a second series, 4 patients received transplants of dispersed pancreatic tissue without islet purification; complete amelioration of diabetes was not achieved in this series either. Islet function has been established in some instances for a brief period, but rejection has occurred. In other instances, islet tissue has not functioned. However, the technical feasibility of islet transplantation has been demonstrated by performance of an islet autotransplant to a patient with chronic pancreatitis who underwent near total pancreatectomy. In this instance, the pancreatic islet tissue was prepared from the excised pancreas and the tissue infused into the portal vein, and the diabetic state was completely obviated. This patient who now has a normal glucose tolerance test and does not require insulin. Thus if rejection can be prevented, transplantation of dispersed pancreatic islet tissue seems feasible. The series of islet allografts will be continued in the coming year, using freshly prepared pancreatic islet tissue transplanted to recipients sharing greater than or equal to 2 HLA antigens with the donor. If the procedure can be perfected to the point where metabolic abnormalities of diabetes can be reversed, the effect on the secondary complications of diabetes will be studied.